The proposed study is designed to characterize local mechanisms of action in the brainstem and stomach during chemically induced changes in gastric wall tension. Many of the substances to be evaluated are peptides which are endogenous to the stomach and region of the brainstem which is involved in the regulation of gastric activity. We are especially interested in determining 1) the neurotransmitter(s) responsible for signaling changes in gastric wall tension to neurons in the brainstem; 2) whether different transmitters are released by passive distention, active contraction and by activation of chemoreceptors; and 3) whether different neurotransmitters are involved in signaling excitatory and inhibitory responses in the brainstem units. The experimental approach taken to address these questions are the local application of selected substances 1) peripherally at the stomach and 2) upon single units in the brainstem which respond to phasic gastric distention. We have developed an animal model which enables us to evaluate brain-gut interactions involving the stomach and the brainstem utilizing chemical probes to characterize local neuronal and chemical mechanisms of action in these structures. To achieve this aim extracellular recordings will be made from single units in a population of neurons which we have identified in the region of nucleus and tractus solitarius in the brainstem of the cat that respond to phasic gastric distention. Hormones, peptides, neurotransmitters and drugs will be used as chemical probes, via local gastric intraarterial injection, to induce changes in wall tension in the stomach which are reflected in the discharge pattern of units in this brainstem population. Microapplication techniques, iontophoresis and pressure, will be used to apply many of these same substances locally upon single neurons in the brainstem during chemically induced changes in gastric activity.